Fridman Wolf H, Meylan Maxime, Pupier Guilhem, Calvez Anne, Hernandez Isaïas, Sautès-Fridman Catherine
Centre de Recherche des Cordeliers, INSERM U1138, Université Paris Cité, Sorbonne Université, 75006 Paris, France; Equipe labellisée Ligue Contre le Cancer (EL 2021), Paris, France.
Centre de Recherche des Cordeliers, INSERM U1138, Université Paris Cité, Sorbonne Université, 75006 Paris, France; Equipe labellisée Ligue Contre le Cancer (EL 2021), Paris, France.
Immunity. 2023 Oct 10;56(10):2254-2269. doi: 10.1016/j.immuni.2023.08.009. Epub 2023 Sep 11.
The generation of anti-tumor immunity in the draining lymph nodes is known as the cancer immunity cycle. Accumulating evidence supports the occurrence of such a cycle at tumor sites in the context of chronic inflammation. Here, we review the role of tertiary lymphoid structures (TLS) in the generation of T and B cell immunities, focusing on the impact of B cells that undergo full maturation, resulting in the generation of plasma cells (PCs) producing high-affinity IgG and IgA antibodies. In this context, we propose that antibodies binding to tumor cells induce macrophage or natural killer (NK)-cell-dependent apoptosis. Subsequently, released antigen-antibody complexes are internalized and processed by dendritic cells (DCs), amplifying antigen presentation to T cells. Immune complexes may also be fixed by follicular DCs (FDCs) in TLS, thereby increasing memory B cell responses. This amplification loop creates an intra-tumoral immunity cycle, capable of increasing sensitivity of tumors to immunotherapy even in cancers with low mutational burden.
引流淋巴结中抗肿瘤免疫的产生被称为癌症免疫循环。越来越多的证据支持在慢性炎症背景下肿瘤部位存在这样一个循环。在这里,我们回顾三级淋巴结构(TLS)在T细胞和B细胞免疫产生中的作用,重点关注经历完全成熟的B细胞的影响,这会导致产生分泌高亲和力IgG和IgA抗体的浆细胞(PC)。在这种情况下,我们提出与肿瘤细胞结合的抗体诱导巨噬细胞或自然杀伤(NK)细胞依赖性凋亡。随后,释放的抗原 - 抗体复合物被树突状细胞(DC)内化和处理,增强向T细胞的抗原呈递。免疫复合物也可能被TLS中的滤泡树突状细胞(FDC)固定,从而增加记忆B细胞反应。这个放大环形成了肿瘤内免疫循环,即使在低突变负荷的癌症中也能够增加肿瘤对免疫疗法的敏感性。
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